Purchase of the LTQ-Orbitrap hybrid mass spectrometer This proposal seeks funding for the purchase of an ultra high performance Thermo Electron LTQ-Orbitrap hybrid MS. The proposed instrument is essential to many NIH funded research programs at UCI as there is no mass spectrometer with the capabilities of the LTQ-Orbitrap MS available on the UCI campus. This instrument provides high sensitivity, resolution, mass accuracy, dynamic range and throughput simultaneously, which will enhance our ability to sequence peptides and proteins for protein identification and comprehensive characterization of posttranslational modifications at the attomole level. The goal is to use mass spectrometry-based proteomics approaches to elucidate the molecular mechanisms underlying the development of various human diseases including cancers. The requested instrument will be used to carry out detailed structure-function analyses of the 26S proteasome complex (Dr. Huang), ubiquitination signaling cascades (Dr. Kaiser), regulatory proteins in cancer (Dr. Lee), retro-virus-like core particles (Dr. Sandmeyer), LEF/TCF -catenin complexes (Dr. Waterman), immune cell ion channel signaling (Dr. Cahalan), cellular factors involved in Huntington disease (Dr. Marsh), dimorphic switching and control of pathogenic forms of C. albicans (Dr. Liu), RNA uridylyltransferases as potential anti-Trypanosome drug targets (Dr. Aphasizhev), and regulation of mitochondria integrity in cancer (Dr. Wallace). The high performance of the new instrumentation will make it possible to determine the composition of disease-related protein complexes and their posttranslational modifications on a routine basis. To ensure maximum usage and proper maintenance, the instrument will be housed in the mass spectrometry laboratory of the PI, Dr. Huang. The PI has over 10 years experience in the area of proteomics/biological mass spectrometry. Dr. Cahalan will chair the Advisory Committee responsible for overall guidance for the shared instrument's use. Dr. Burlingame will serve as an external Advisory Committee member. Dr. Huang will discuss experimental strategies with investigators, oversee optimization of performance and prioritize scheduling. Her staff member will provide daily supervision of usage, training and maintenance. UCI has agreed to provide $150k for the purchase of the proposed instrument, and additional financial support for the instrument's maintenance and an instrument operator for four years. The ten principal Investigators are involved in 26 NIH-supported research programs with growing needs for cutting-edge technology for their proteomics research related to human health and diseases. The requested instrument would represent an important advance for biomedical research in the UCI Schools of Medicine and Biological Sciences as a shared interdisciplinary resource for members of five different departments. [unreadable] [unreadable] [unreadable]